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Increased expression of fatty acid synthase and acetyl-CoA carboxylase in the prefrontal cortex and cerebellum in the valproic acid model of autism

View Article: PubMed Central - PubMed

ABSTRACT

The primary aim of the present study was to investigate alterations in enzymes associated with fatty acid synthesis, namely fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC), in the prefrontal cortex and cerebellum of the valproic acid (VPA)-induced animal model of autism. In this model, pregnant rats were given a single intraperitoneal injection of VPA, and prefrontal cortex and cerebellum samples from their pups were analyzed. The results of western blotting and reverse transcription-quantitative polymerase chain reaction analyses demonstrated that the protein and mRNA expression levels of FASN, ACC and phospho-ACC (pACC) were increased in the prefrontal cortex and cerebellum of the VPA model of autism. Furthermore, in the prefrontal cortex and cerebellum of the VPA model of autism, AMPK expression is increased, whereas PI3K and Akt expression are unchanged. This suggests that disorder of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt/FASN and/or adenosine 5′-monophosphate-activated protein kinase (AMPK)/ACC pathway may be involved in the pathogenesis of autism. It is hypothesized that fatty acid synthesis participates in autism through PI3K/Akt/FASN and AMPK/ACC pathways.

No MeSH data available.


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Signaling molecule protein expression in the cerebellum of the valproic acid (VPA) model of autism. (A) Western blot of the cerebellum in the VPA model of autism. (B) Quantification of the immunoblots following normalization using β-actin. The data are shown as the mean ± standard error of the mean (n=8). *P<0.05, **P<0.01 for the VPA group vs. the control. Significant differences between the VPA and control groups were identified by independent-samples t-test. ACC, acetyl-coenzyme A carboxylase; pACC, phospho-ACC; FASN, fatty acid synthase; AMPK, adenosine 5′-monophosphate-activated protein kinase; PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase.
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f2-etm-0-0-3508: Signaling molecule protein expression in the cerebellum of the valproic acid (VPA) model of autism. (A) Western blot of the cerebellum in the VPA model of autism. (B) Quantification of the immunoblots following normalization using β-actin. The data are shown as the mean ± standard error of the mean (n=8). *P<0.05, **P<0.01 for the VPA group vs. the control. Significant differences between the VPA and control groups were identified by independent-samples t-test. ACC, acetyl-coenzyme A carboxylase; pACC, phospho-ACC; FASN, fatty acid synthase; AMPK, adenosine 5′-monophosphate-activated protein kinase; PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase.

Mentions: To evaluate the expression changes of FASN in autism, a VPA model of autism was generated. Western blot analysis showed a 4-fold increase in FASN protein expression in the prefrontal cortex and a 2-fold increase in FASN expression in the cerebellum in the VPA group. The relative expression values (FASN/β-actin) were 0.76±0.02 for the VPA group and 0.17±0.01 for the control group in the prefrontal cortex (Fig. 1), and 0.76±0.06 for the VPA group and 0.33±0.03 for the control group in the cerebellum (Fig. 2). Using RT-qPCR, it was detected that the mRNA level of FASN in the VPA group was 6.1-fold higher than that of the control group in the prefrontal cortex (Fig. 3) and 2.8-fold higher than that of the control group in the cerebellum (Fig. 4).


Increased expression of fatty acid synthase and acetyl-CoA carboxylase in the prefrontal cortex and cerebellum in the valproic acid model of autism
Signaling molecule protein expression in the cerebellum of the valproic acid (VPA) model of autism. (A) Western blot of the cerebellum in the VPA model of autism. (B) Quantification of the immunoblots following normalization using β-actin. The data are shown as the mean ± standard error of the mean (n=8). *P<0.05, **P<0.01 for the VPA group vs. the control. Significant differences between the VPA and control groups were identified by independent-samples t-test. ACC, acetyl-coenzyme A carboxylase; pACC, phospho-ACC; FASN, fatty acid synthase; AMPK, adenosine 5′-monophosphate-activated protein kinase; PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998172&req=5

f2-etm-0-0-3508: Signaling molecule protein expression in the cerebellum of the valproic acid (VPA) model of autism. (A) Western blot of the cerebellum in the VPA model of autism. (B) Quantification of the immunoblots following normalization using β-actin. The data are shown as the mean ± standard error of the mean (n=8). *P<0.05, **P<0.01 for the VPA group vs. the control. Significant differences between the VPA and control groups were identified by independent-samples t-test. ACC, acetyl-coenzyme A carboxylase; pACC, phospho-ACC; FASN, fatty acid synthase; AMPK, adenosine 5′-monophosphate-activated protein kinase; PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase.
Mentions: To evaluate the expression changes of FASN in autism, a VPA model of autism was generated. Western blot analysis showed a 4-fold increase in FASN protein expression in the prefrontal cortex and a 2-fold increase in FASN expression in the cerebellum in the VPA group. The relative expression values (FASN/β-actin) were 0.76±0.02 for the VPA group and 0.17±0.01 for the control group in the prefrontal cortex (Fig. 1), and 0.76±0.06 for the VPA group and 0.33±0.03 for the control group in the cerebellum (Fig. 2). Using RT-qPCR, it was detected that the mRNA level of FASN in the VPA group was 6.1-fold higher than that of the control group in the prefrontal cortex (Fig. 3) and 2.8-fold higher than that of the control group in the cerebellum (Fig. 4).

View Article: PubMed Central - PubMed

ABSTRACT

The primary aim of the present study was to investigate alterations in enzymes associated with fatty acid synthesis, namely fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC), in the prefrontal cortex and cerebellum of the valproic acid (VPA)-induced animal model of autism. In this model, pregnant rats were given a single intraperitoneal injection of VPA, and prefrontal cortex and cerebellum samples from their pups were analyzed. The results of western blotting and reverse transcription-quantitative polymerase chain reaction analyses demonstrated that the protein and mRNA expression levels of FASN, ACC and phospho-ACC (pACC) were increased in the prefrontal cortex and cerebellum of the VPA model of autism. Furthermore, in the prefrontal cortex and cerebellum of the VPA model of autism, AMPK expression is increased, whereas PI3K and Akt expression are unchanged. This suggests that disorder of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt/FASN and/or adenosine 5&prime;-monophosphate-activated protein kinase (AMPK)/ACC pathway may be involved in the pathogenesis of autism. It is hypothesized that fatty acid synthesis participates in autism through PI3K/Akt/FASN and AMPK/ACC pathways.

No MeSH data available.


Related in: MedlinePlus